Bone morphogenic protein receptor type 1a (BMPR1A) and Caveolin-1 associated with trastuzumab resistance of breast cancer cells

Trastuzumab is a specific monoclonal antibody used for therapeutic of the human epidermal growth factor receptor 2 (HER-2) -positive metastatic breast cancer. But, resistance to trastuzumab is a major obstacle in clinical efficiency.  During the past years, several studies have been done to find the mechanisms contributing to trastuzumab resistance. Previous studies have highlighted that bone morphogenic protein (BMP) signaling can indicate a pathway in cancer for sensitizing cells to chemotherapy. Also, it was suggested that Caveolin-1 is essential for the formation of caveolae and endocytic membrane transport and has a critical role in drug resistance and metastasis in cancer. The purpose of this study was to assess the expression of BMP receptor type1A (BMPR1A) and Caveolin-1 genes in compare with trastuzumab-sensitive and resistance BT-474 cells. Trastuzumab-resistant BT474 cells were established by continuous subjection to trastuzumab for six months. Then, an MTT assay was done for determining the resistance. After that, the Expression of BMPR1A and Caveolin-1levels were assessed through real-time PCR. Caveolin-1 expression levels increased significantly (2.4 fold, p<0.05) whereas BMPR1A levels down-regulated significantly (8.26 fold, p<0.05) in BT474-R compared to the parental cells. Our results proposed that BMPR1A and CAV1 regulation take part in BT-474 trastuzumab resistance breast cancer. Therefore, further experiments are required to confirm the role/s of BMPR1A and CAV1 in trastuzumab resistance breast cancer.